Purpose <p>Segmentation of breast lesions in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is critical for effective diagnosis. This study investigates the impact of breast region segmentation (BRS) on the performance of deep learning-based breast lesion segmentation (BLS) in breast DCE-MRI.</p> Methods <p>The study utilized the Stavanger Dataset, comprising 59 DCE-MRI scans, and employed the UNet++ architecture as the segmentation model. Four experimental approaches were designed to assess the influence of BRS on BLS: (1) Whole Volume (WV) without BRS, (2) WV with BRS, (3) BRS applied only to Selected Lesion-containing Slices (SLS), and (4) BRS applied to an Optimal Volume (OV). Data augmentation and oversampling techniques were implemented to address dataset limitations and enhance model generalizability. A systematic method was employed to determine OV sizes for patient’s DCE-MRI images ensuring full lesion inclusion. Model training and validation were conducted using a hybrid loss function—comprising Dice loss, focal loss, and cross-entropy loss—and a five-fold cross-validation strategy. Final evaluations were performed on a randomly split test dataset for each of the four approaches.</p> Results <p>The findings indicate that applying BRS significantly enhances model performance. The most notable improvement was observed in the fourth approach, BRS with OV, which achieved approximately a 50% increase in segmentation accuracy compared to the non-BRS baseline. Furthermore, the BRS with OV approach resulted in a substantial reduction in computational energy consumption—up to 450%, highlighting its potential as an environmentally sustainable solution for large-scale applications.</p>